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Physiol. Genomics (January 11, 2005). doi:10.1152/physiolgenomics.00228.2003
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Submitted on December 29, 2003
Accepted on January 9, 2005

Assessing natural variations in gene expression in humans by comparing with monozygotic twins using microarrays

Anu Sharma1, Vineet K Sharma2, Shirley Horn-Saban3, Doron Lancet4, Srinivasan Ramachandran5*, and Samir K Brahmachari5

1 Functional Genomics Unit, Institute of Genomics and Integrative Biology, Delhi, India
2 G.N. Ramachandran Knowledge Center for Genome Informatics, Institute of Genomics and Integrative Biology, Delhi, India
3 Microarray Facility, Department of Biological Services, The Weizmann Institute of Science, Rehovot, Israel
4 Department of Molecular Genetics and Crown Human Genome Center, The Weizmann Institute of Science, Rehovot, Israel
5 Functional Genomics Unit, Institute of Genomics and Integrative Biology, Delhi, India; G.N. Ramachandran Knowledge Center for Genome Informatics, Institute of Genomics and Integrative Biology, Delhi, India

* To whom correspondence should be addressed. E-mail: ramu{at}igib.res.in.

Quantitative variation in gene expression in humans is the outcome of various factors including differences in genetic background, gender, age and environment. However, the extent of the influence of these factors on gene expression is not clear. We attempted to address this issue by carrying out gene expression profiling in blood leukocytes with thirteen individuals (including five pairs of monozygotic twins) on 10,000 genes using HG U95Av2 oligonucleotide microarrays. The proportion of differentially expressed genes between monozygotic twins was low (upto 1.76%). Most of the variations belonged to the least variable category. These genes exhibiting 'random variations' did not show clear preference to any functional class, although 'signaling and communication' and 'immune and related functions' generally topped the list. The extent of variation in gene expression increased in comparisons between unrelated individuals (upto 14.13%). Most of the genes (89%) exhibiting random variations in twins also varied in expression in unrelated individuals. As with twins, 'signaling and communication' topped the list and substantial variations were observed in all three categories: least variable, moderately variable and most variable. An important outcome of this study was that the housekeeping genes were nearly insensitive to random variations but appeared to be more susceptible to genetic differences. However, the highly expressed housekeeping genes exhibited low variation and appeared to be insensitive to all known factors. Gene expression profiling in monozygotic twins can provide useful data for assessment of natural variation in gene expression in humans.




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